The biochemical and physiological effects of Gs activation are well known however, little is known about the anatomical localisation of Gs in the myocardium. Knowledge of the localisation might yield insights into G protein function in heart. The utility of immunocytochemistry using immunofluorescent methods is limited in normal hearts because of the low expression of Gs. In order to magnify the Gs signal, we studied transgenic mice overexpressing myocardial Gs. Immunofluorescent labeling appeared to be localized to the T-tubules and intercalated disks in the Gs overexpressing mouse hearts, whereas the control mice showed background fluorescence with diffuse faint labeling. The localisation of Gs to structures involved in calcium handling and membrane conductance